Heterozygous variants inACTL6A, encoding a component of the BAF complex, are associated with intellectual disability
Year: 2017
Type: article
Study design: Case Report
Abstract: Pathogenic variants in genes encoding components of the BRG1-associated factor (BAF) chromatin remodeling complex have been associated with intellectual disability syndromes. We identified heterozygous, novel variants in ACTL6A, a gene encoding a component of the BAF complex, in three subjects with varying degrees of intellectual disability. Two subjects have missense variants affecting highly conserved amino acid residues within the actin-like domain. Missense mutations in the homologous region in yeast actin were previously reported to be dominant lethal and were associated with impaired binding of the human ACTL6A to β-actin and BRG1. A third subject has a splicing variant that creates an in-frame deletion. Our findings suggest that the variants identified in our subjects may have a deleterious effect on the function of the protein by disturbing the integrity of the BAF complex. Thus, ACTL6A gene mutation analysis should be considered in patients with intellectual disability, learning disabilities, or developmental language disorder.
Source: Human Mutation
DOI: 10.1002/humu.23282
Authors: Ronit Marom, Mahim Jain, Lindsay C. Burrage, I-Wen Song, Brett H. Graham, Chester W. Brown, Servi J.C. Stevens, Alexander P.A. Stegmann, Andrew T. Gunter, Julie D. Kaplan, Ralitza H. Gavrilova, Marwan Shinawi, Jill A. Rosenfeld, Yangjin Bae, Alyssa A. Tran, Yuqing Chen, James T. Lu, Richard A. Gibbs, Christine Eng, Yaping Yang, Justine Rousseau, Bert B.A. de Vries, Philippe M. Campeau, Brendan Lee
Institutions: Baylor College of Medicine, University of Tennessee Health Science Center, Maastricht University Medical Centre, University of Mississippi Medical Center, Mayo Clinic, Washington University in St. Louis, Helix (United States), Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Radboud University Nijmegen, Radboud University Medical Center, Donders Centre for Neuroscience
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Osteogenesis Imperfecta Foundation, ACMG Foundation for Genetic and Genomic Medicine, ZonMw, National Institutes of Health, Intellectual and Developmental Disabilities Research Center, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Baylor-UT Houston Center for AIDS Research, G1707684326, Baylor-Johns Hopkins Center for Mendelian Genetics, BD Biosciences Special Order LSRII, The Human Genome Sequencing Center, G5033718190, Baylor Intellectual and Developmental Disabilities Research Center, Disordered Energy Metabolism in Argininosuccinate Lyase Deficiency, G7189771219, Pathogenesis of Novel Forms of Osteogenesis Imperfecta, Medical Genetics Research Fellowship Program, Baylor College of Medicine Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2682847713